Iontophoresis methods

ABSTRACT

A method of anesthetizing a tympanic membrane of an ear of a patient using iontophoresis is disclosed. The method involves delivering an anesthetizing drug solution to an ear canal of the patient&#39;s ear, wherein the drug solution includes an anesthetic and a buffer, and wherein the drug solution has a pH in the range of about 6.5 to about 7.5; and applying an amount of current to the drug solution, wherein the amount of applied current is increased at a rate of less than about 0.5 milliamp per second until a maximum current is achieved.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of and claims priority to U.S. patentapplication Ser. No. 13/467,851, filed May 9, 2012, entitled“Iontophoresis Methods,” which is a divisional of and claims priority toU.S. patent application Ser. No. 11/962,063, filed Dec. 20, 2007,entitled “Iontophoresis Methods,” now U.S. Pat. No. 8,192,420, thecontents of each of which are incorporated herein by reference in theirentirety.

TECHNICAL FIELD

The present invention is related to iontophoretic drug delivery methodsand systems. In particular, the present invention is related to noveland advantageous iontophoretic drug delivery methods and systems foranesthetizing ear tissue.

BACKGROUND

Iontophoresis is a method for delivering a drug across a biologicalmembrane, such as the skin or, in the case of certain ear surgeryprocedures, the tympanic membrane (TM). By applying low-level electricalcurrent to a similarly charged drug solution, iontophoresis repels ionsof the drug, thus transporting them across the skin or other membrane.In ear procedures, attempts have been made in the past to useiontophoresis to anesthetize (or “numb”) a TM before placing an ear tubeacross it to treat chronic ear infections. For TM iontophoresis, a drugsolution is placed in an ear canal and current is applied to thesolution, thus transporting the anesthetizing drug across the TM.

In theory, iontophoresis should be ideal for numbing a TM, because itwould allow drug to be transported across the full thickness of the TM,would focus the drug delivery on the TM and the surrounding ear canal,and would not require a painful injection with a needle. Iontophoreticdrug delivery to the TM has proven challenging, however. Companies suchas Xomed, Inc. (Medtronic Xomed, Inc.) and Otomed, Inc. (Lake HavasuCity, Ariz.) have previously provided iontophoresis systems foranesthetizing TMs, but these systems and their associated methods havehad a number of significant drawbacks. Most significantly, it has beenvery challenging, using previous iontophoresis systems, to provideadequate anesthesia to the TM without causing significant pain anddiscomfort to the patient in the process. Although the pain anddiscomfort caused by applying current to an iontophoretic solution inthe ear canal may range from mild to severe, even mild pain ordiscomfort may make an ear tube placement procedure intolerable forpediatric patients and even some adult patients.

To drive a drug solution across a TM via iontophoresis, the solutionmust have certain characteristics to allow it to be transported, andcurrent must be applied in such a way to cause the transport. Previouslyused iontophoresis solutions for TM anesthesia were generally mixturesof lidocaine and epinephrine, often having a pH range of about 5.2-5.9,and this pH range was thought to be optimal for iontophoretic drugdelivery. Once the solution is in place in the ear canal, a sufficientamount of current must be applied for a sufficient amount of time totransport the anesthetizing drug across the TM. Unfortunately, withpreviously available systems, the combinations of drug solution andcurrent application were typically at least uncomfortable and oftenquite painful. Attempts to decrease the pain caused by iontophoresisgenerally resulted in unsatisfactory drug delivery.

Placement of ear tubes through the TMs for treating chronic earinfections is one of the most common ear, nose and throat (“ENT” or“otolaryngology”) surgical procedures requiring general anesthesia inchildren. Although tube placement is a relatively routine procedure, italmost always requires general anesthesia when performed on children,since they are usually unable to tolerate the pain and discomfortassociated with numbing the tympanic membranes for the procedure.Unfortunately, general anesthesia carries a number of risks, some ofwhich are still unknown and being researched. Adult patients sometimesundergo ear tube placement with topical applications of local anesthesia(such as phenol), thus avoiding general anesthesia, but oftentimes sucha procedure is quite painful or at least very uncomfortable, due tounsatisfactory methods of numbing the TMs. Therefore, it would be highlyadvantageous to provide a method for anesthetizing TMs and surroundingear tissue that would eliminate the need for general anesthesia and thatwould be palatable to patients.

Therefore, a need exists for improved iontophoretic methods and systems.Ideally, such methods and systems would facilitate iontophoretic drugdelivery across a tympanic membrane for ear tube placement or othersurgical procedures in the ear. Also ideally, such methods and systemswould minimize or eliminate any pain caused by the iontophoresisprocess. At least some of these objectives will be met by the variousembodiments of the present invention.

SUMMARY

The present invention is directed to novel and advantageousiontophoretic drug delivery methods and systems, which may be used byENT surgeons to anesthetize tympanic membranes (TMs). Variousembodiments include means for providing simultaneous bilateralanesthetization of the TMs, reduction in patient discomfort via controlof applied current, current density and ramp rate, allowance forintervention during the procedure by a physician, enhanced and real-timemonitoring of the output current, and/or collection of the system'soperational data.

In one embodiment, the present invention provides a method ofanesthetizing a tympanic membrane of an ear of a patient usingiontophoresis. The method may involve delivering an anesthetizing drugsolution to an ear canal of the patient's ear, wherein the drug solutionincludes an anesthetic and a buffer, and wherein the drug solution has apH in the range of about 6.5 to about 7.5; and applying an amount ofcurrent to the drug solution, wherein the amount of applied current isincreased at a rate of less than about 0.5 milliamp per second until amaximum current is achieved.

In one aspect, the anesthetic may include lidocaine and the buffer mayinclude sodium bicarbonate, and wherein the solution also includesepinephrine. The drug solution may include approximately 2%-4% lidocaineby weight. The drug solution may include approximately 0.5%-

In one aspect, the drug solution may have a pH range of about 6.8-7.2.

In another aspect, the application of the current may involve increasingthe amount of applied current at a rate of about 0.2 milliamps persecond.

In another aspect, the application of the current may involve applying amaximum current of approximately 1.0 milliamp or less. In anotheraspect, the application of the current may involve applying a maximumcurrent of approximately 0.8 milliamps or less.

In another embodiment, the present invention provides a method ofanesthetizing a tympanic membrane of an ear of a patient usingiontophoresis. The method may involve adding buffer to an anesthetizingdrug solution for iontophoresis, wherein the drug solution with addedbuffer has a pH in the range of about 6.5 to about 7.5; delivering thebuffered anesthetizing drug solution to an ear canal of the patient'sear; and applying an amount of current to the drug solution, wherein theamount of applied current is increased at a rate of less than about 0.5milliamp per second until a maximum current of less than about 0.5milliamp is achieved.

In one aspect, the buffered drug solution has a pH range of about6.8-7.2.

In another aspect, the application of the current may involve increasingthe amount of applied current at a rate of about 0.2 milliamps persecond.

In another aspect, the application of the current may involve applying amaximum current of approximately 0.8 milliamps or less.

In another embodiment, the present invention provides a method oftreating a patient, the patient having a first and a second ear canal.The method may involve positioning a fluid in the first ear canal, thefluid comprising a therapeutic agent; positioning a fluid in the secondear canal, the fluid comprising a therapeutic agent; inserting a firstelectrode of an iontophoresis device in the first ear canal; inserting asecond electrode of the iontophoresis device in the second ear canal;attaching one ground electrode of the iontophoresis device to thepatient, the first electrode and the one ground electrode forming afirst circuit, the second electrode and the same one ground electrodeforming a second circuit; applying the agent from the fluid to a targettissue in the first ear canal by energizing the first circuit to delivera current to the agent in the first ear canal; and applying the agentfrom the fluid to a target tissue in the second ear canal by energizingthe second circuit to deliver a current to the agent in the second earcanal, independently of the applying in the first circuit.

In one aspect, the agent may include an anesthetic.

In another aspect, the agent may include at least one of lidocaine,epinephrine, sodium bicarbonate, other anesthetics, other buffers, orcombinations thereof.

In another aspect, the agent may include at least one of an antibiotic,an anti-inflammatory, a mucolytic, an anesthetic, a steroid, ananti-viral, a surfactant or combinations thereof.

In another aspect, the energizing of the first or the second circuit mayinclude applying a current to the agent over a time period, the currenthaving an initial value, a final value, a ramp-up rate from the initialvalue to the final value and a ramp-down rate from the final value tothe initial value. The ramp-up rate is about 0.2 milliamps per second.The ramp-up rate may have a stepped and positive slope. The final valuemay be less than about 1.0 milliamp. The period of time may be betweenabout 30 and 240 seconds.

In another aspect, the method may also involve pausing the applicationof the agent during the application.

In one aspect, the fluid is an iontophoretic solution of lidocaine andepinephrine that is buffered to have a pH of about 6.8-7.2.

In another aspect, the iontophoretic solution may have a lidocaine HClconcentration between approximately 2%-4% by weight.

In another aspect, the method may also include monitoring the first orthe second circuit's output current. In one aspect, the monitoring mayinvolve comparing the output current with a threshold value. In anotheraspect, the monitoring may be performed at a rate of at least once persecond.

In another embodiment, the present invention provides an iontophoresissystem for anesthetizing a tympanic membrane of an ear of a patient. Thesystem may include an anesthetizing drug solution including ananesthetic and a buffer and having a pH in the range of about 6.5 toabout 7.5; a current source; and a controller coupled with the currentsource, the controller programmed to increase an amount of currentapplied to the drug solution at a rate of less than about 0.5 milliampper second until a maximum current of less than about 1.0 milliamp isachieved.

In one aspect, the anesthetizing drug solution may include ananesthetic, epinephrine and a buffer. The drug solution may haveapproximately 2%-4% of lidocaine by weight and approximately 0.5%-1.0%of sodium bicarbonate by weight.

In another aspect, the drug solution may have a pH range of about6.8-7.2.

In another aspect, the controller may be programmed to increase theamount of current applied to the drug solution at a rate of about 0.2milliamps per second until a maximum current of about 0.8 milliamps isachieved.

In another aspect, the current source may include at least one earelectrode configured for placement in an ear canal of the patient.

In another aspect, the current source may include two ear electrodesconfigured for placement in two ear canals of the patient, thus allowingfor approximately simultaneous application of current to anesthetizingdrug solution disposed in the two ear canals.

For further understanding of the nature and advantages of the variousembodiments, reference should be made to the following description takenin conjunction with the accompanying figures. Each of the figures isprovided for the purpose of illustration and description only and is notintended to limit the scope of the embodiments of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an exemplary iontophoresis system, according to oneembodiment of the present invention.

FIG. 2 is an exemplary circuit diagram illustrating the electronicarchitecture of the iontophoresis system of FIG. 1.

FIG. 3 illustrates exemplary sensometers that may be operatively coupledwith an iontophoresis system, according to one embodiment of the presentinvention.

FIG. 4 illustrates an exemplary current ramp rate for an iontophoresissystem, according to one embodiment of the present invention.

DETAILED DESCRIPTION

According to various embodiments, an iontophoresis method and system mayprovide ear, nose and throat (“ENT”) surgeons (also called“otolaryngologists”) with an improved means for anesthetizing tympanicmembranes (TMs). An exemplary iontophoresis system that may be enhancedusing embodiments of the present invention is described in theassignee's co-pending patent application Ser. No. 11/749,729, entitled“Disposable Iontophoresis System and Tympanic Membrane Pain InhibitionMethod,” which is incorporated fully herein by reference. Certainaspects of that system are described below.

FIGS. 1-2 are used to illustrate various aspects of an iontophoresissystem 300, according to one embodiment. As shown in FIG. 1,iontophoresis system 300 may include a battery powered disposableelectronic device 310 having an LCD display 308 one or more buttons 312for operation, two electrodes (one for each ear) 302A-B coupleable withdevice 310, and a return electrode patch 306 coupleable with device 310.Device 310 may be configured to deliver regulated current to electrodes302A-B. Each electrode 302A-B may be configured to fit within anexternal ear canal or a guide block that is positioned in the ear canal.Each electrode 302A-B may be configured to conform to the shape of apatient's ear canal and thus retain a drug solution in the canal whiledelivering electrical current to the solution. Various embodiments ofelectrodes 302A-B may be sized to fit patients ranging in age from 12months to adult. Return electrode 306 may be attached to the patient'sskin to complete the electrical circuit. As shown in FIG. 1, theiontophoresis system 300 may be a small electronic device, in variousembodiments ranging from about the size of a business card to the sizeof an iPod™ or personal digital assistant. In one embodiment, device 310may be co-located with return electrode patch 306 to minimize the amountof loose wires and overall package size. In this embodiment, returnelectrode patch 306 may be attached permanently or by means of a metalsnap or other electrically conductive attachment mechanism to device310, and device/patch 310/306 may be adhered to the patient's skin (e.g.at the back of the neck) via return electrode patch 306, thereby fixingthe device 310 in a location easily accessible to the physician but noteasily accessible to the patient.

In one embodiment, iontophoresis system 300 may be activated by pullinga small plastic tab (not shown) from the back of device 310. Such a tabmay be configured to keep batteries installed in device 310 frompowering the device circuitry until desired. When the tab is pulled, thebatteries begin powering the circuitry and the LCD 308 may illuminate.In alternative embodiments, any other suitable means for powering device310 may be included, such as a power switch or button.

In various embodiments, device 310 may be powered before or afterapplying return electrode 306 to the patient. At some point, a solutionis placed in the patient's ear canal, an electrode 302A-B is placed inthe canal, and electrode 302A-B is used to apply current to thesolution. In some embodiments, electrode 302A-B may be placed in thecanal before solution is placed, and the solution may then be passedinto the canal through or around electrode 302A-B, such as when a guideblock is used. In some embodiments, solution may be placed in one ear,an electrode 302A may be positioned in that ear canal, solution may beplaced in the other ear, an electrode 302B may be placed in that ear,and then iontophoresis may be performed on both ears simultaneously,almost simultaneously, or sequentially. Alternatively, a left electrode302A may be placed first, and a “Left Ear Start” button on device 310may be pressed to begin an automatic, pre-programmed current deliverysequence. A right ear electrode 302B may then be placed into thepatient's right ear canal and a “Right Ear Start” button may be pressedto independently begin current delivery to the right ear. In someembodiments, a progress meter may be displayed for each ear on LCD 308.For example, a progress meter may be represented by a filled-in area ofa box, which starts empty and fills in as current is delivered until isit fully filled and the process is complete. Once current deliverystarts, the user can wait for the device to signal it is finished orthere is a problem via an auditory beep sound. After the device deliversthe full dosage of current to each ear, the progress meter for each earis filled and the system can deliver a short series of beeps to signalsuccessful completion. Once the device signals it is completed it canautomatically shut down. At this point, the user can remove theelectrodes, and can start the process of removing any iontophoresissolution remaining in the ear canal. Again, this can be doneindependently on one side without affecting proper device operation onthe other side.

At any time during the process, the current delivered to an electrodecan be paused, for example by pressing the left or right button. Thesystem can then ramp down the current to that electrode. The user canalso pause both electrodes at once, for example by pressing the stopbutton. This will cause the system to ramp down the current to bothelectrodes. In either case the user can continue with the procedure bypressing the left or right buttons. This will cause the system to rampup the current for that electrode and continue delivering the totalcharge where it left off before being paused. In one embodiment, thesame button may be used for starting, pausing and stopping currentdelivery to an electrode, while in alternative embodiments separatestart, pause and/or stop buttons may be included.

At the end of the iontophoresis current delivery cycle, the current willramp down to zero. Once both sides have completed iontophoresis and theelectrodes have been removed, the return patch can also be removed andthe entire unit discarded. Power can automatically shut off after onehour of time, or any selected unit of time. The unit can be designed toallow only one use and cannot be turned back on. Another embodimentdisables the current delivery function after a single use, but thenenables additional functionality, such as a game, a clock, etc. for thepatient's use after the procedure.

In some embodiments, if an error occurs during a procedure, the systemmay emit an indicator signal, such as a series of long beeps.Alternatively, or in addition to the series of long beeps, visual meansmay be used, so as not to disturb the patient. For example, a blinkinglight located on the back of the unit or other hard to reach place wouldlikely not be noticed by patient. Conditions that could cause such anerror include: a detected open circuit or an over current condition. Inthe case of an open circuit, the device may automatically stopdelivering current to the patient through a controlled current ramp downand the user may resume delivery by pressing a start button on thedevice. In the case of over current, the device may detect an internalerror, automatically stop all current to both electrodes, and notrestart, at which point the device may be discarded. In someembodiments, an indicator message may be displayed on LCD screen 308.

Referring now to FIG. 2, a circuit diagram illustrating one embodimentof an electronic architecture for iontophoresis system 300 is shown. Inone embodiment, once the plastic tab is removed from the back of device310, two 3V batteries begin to power the circuit. The batteries maysupply a LP2975 voltage regulator, which delivers a stable 5V output.The 5V output is used to supply the microprocessor (e.g., Atmel ATtiny261), the digital-to-analog converter (DAC) converter (e.g., MaximMCP4922), the current sensing operational amplifiers (e.g., LM358), andall components of the operator interface (buttons, buzzer, LCD). Themicroprocessor controls the majority of the functions of the emergencystop button to ramp down current to both electrodes; analog inputs forsensing current delivered to each electrode; serial peripheral interface(SPI) communications to set reference for the DAC; control signals forbuzzer and LCD. External to the microprocessor, the 6V battery powerdrives the MAX5028 DC-DC converter which converts the battery voltage toa 30V output. This output is used as the rail power for the constantcurrent unit. The constant current unit can be designed using one of twoalternatives. The first alternative uses an Operational Amplifier(Op-Amp) such as LM358 which converts a differential input voltage (thecontrol signal) to an output voltage, and eventually to a current basedon the chosen sense resistor. The second technique uses OperationalTransconductance Amplifiers (OTA) which operate in a manner similar toan Op-Amp in that it is controlled by a differential input voltage, butit drives an output current based on a biasing current providedexternally.

The microprocessor sets a reference voltage level to the current sourceusing a DAC. The microprocessor communicates to the DAC via a serialprotocol SPI. The constant current source uses a control signal (0-5V)from the microprocessor to ramp 0 to 1 mA of current according to apredetermined ramp shape. The DC-DC converter provides a high enoughrail voltage (30V) to allow the constant current source to drive 1 mA ofcurrent based on a maximum expected body resistance of 22.5 kOhms. Afterthe allotted delivery time, the microprocessor ramps the control signalback down to 0V, which reduces the current delivered by the currentsource back to zero.

The system may include an LM358 Op-Amp on each electrode line to measurethe current delivered to the patient. The Op-Amps are connected toanalog-to-digital converters internal to the microprocessor. This givesfeedback information to the microprocessor for sensing of open circuitswithin the electrode circuit and to calculate total charge delivered tothe patient. For safety, the current sensing Op-Amps in parallel withthe output electrode also drive an over current monitor. If a faultoccurs and current increases beyond a set limit of 1.5 mA due to someinternal failure, the transistor in the over current shunt will open andallow the increased current to bypass the load, the patient in thiscase, and safely return to the cathode (negative terminal) of thebattery. The microprocessor will independently detect the over currentcondition, shut down the current source, and inform the operator of asystem fault.

After the system has completed delivering the total charge to thepatient it can go into a finished state and begin a timeout count. Atthe end of the timeout count, the firmware may turn off the system suchthat it cannot be turned back on. The microprocessor may include EEPROMmemory written to when the system is turned on initially. If the systemis re-powered, for instance, by forcibly replacing the batteries, thefirmware can detect that it has been powered before and could not turnon again. This scheme is to ensure the device is used only one time. Themicroprocessor includes internal brown-out detection to detect if thesystem voltage is below nominal This detection is used by the firmwareto disallow the system to begin or complete operation if the system doesnot have enough power (e.g. if the batteries are drained).

As described above, the iontophoresis generator may provide twoindependent channels of positive electrical current and a single sharedreturn electrode. Current may be ramped up to a set point and maintaineduntil sufficient charge has been delivered to the drug solution. Thecurrent may then be ramped down, and the system may inform the physicianthat current delivery is complete. In various embodiments, the physicianmay stop or pause the procedure at any time. In some embodiments, thephysician may stop the procedure immediately (i.e., without ramping downcurrent delivery) by simply removing the electrode from the ear canal.

Thus, in some embodiments, the iontophoresis system has two independentchannels, each with its own ear electrode and sharing a single commonreturn electrode. This allows each TM to be anesthetized independentlybut also at the same time, decreasing the amount of time required forthe procedure. The simultaneous bilateral delivery of iontophoresis cancut the procedure time roughly in half when compared with how theexisting devices are used. This is especially useful in reducing thetime children are asked to sit still and tolerate devices in their ears.

Referring now to FIG. 4, in some embodiments, current ramp rate of aniontophoresis method may be configured to minimize or eliminate patientpain and discomfort while still providing sufficient current totransport a drug solution across a TM within a desired amount of time.In some embodiments, an iontophoresis method may involve a slowercurrent “ramp rate” (rate at which the amount of delivered current isincreased) and thus a longer current ramp-up period. In someembodiments, for example, delivered current may increase from zero at arate of less than about 0.5 mA/sec and even more ideally at a rate ofabout 0.2 mA/sec. In some embodiments, total ramp-up time (from zerocurrent delivered to maximum current delivered) may be from about 2minutes to about 5 minutes and even more ideally from about 3 minutes toabout 4 minutes. Maximum current delivered may vary according to variousembodiments, for example in some embodiments it may range from about 0.5mA to about 1.0 mA and even more preferably between about 0.7 mA andabout 0.9 mA and even more preferably about 0.8 mA. The maximum currentmay be maintained for any suitable desired amount of time to achieve TManesthesia, such as from less than one minute to over ten minutes and insome embodiments for example from about five minutes to about eightminutes. Any suitable ramp-down time for the current may be used at theend of iontophoretic current delivery, such as in one embodiment fromless than one minute to about two minutes. In one embodiment, a totaltime for iontophoresis of one TM may take between about five minutes andabout fifteen minutes and even more preferably between about sevenminutes and about twelve minutes.

In some embodiments, the iontophoresis system may be configured to allowa physician to easily respond to patient discomfort by pausing orramping down the device. For example, pressing a single button may pausethe current ramp-up until the physician presses the button again.Pressing a single button for a longer period of time may ramp thecurrent output back down to zero and may keep track of the chargedelivered, allowing the physician to resume the procedure instead ofstarting over.

In some embodiments, a drug solution provided for TM iontophoresis maybe configured to minimize or eliminate pain and discomfort. Because ithas been found that iontophoresis current delivered through an acidiciontophoresis solution may be more painful than current deliveredthrough a more neutral solution, in some embodiments a solution with amore neutral pH may be provided. In one embodiment, for example, abuffer may be added to a conventional iontophoresis solution oflidocaine and epinephrine. Examples of buffers that may be used includebut are not limited to sodium bicarbonate. For example, some previouslyused iontophoresis solutions may have included lidocaine (4%) andEpinephrine (1:1000), with a pH in the range between 5.2-5.9.Epinephrine is packaged in an acidic solution (e.g., {tilde over ( )}3.0pH) to extend its shelf life, but it is stable at higher pH levels forthe duration of time that iontophoresis takes place. Therefore, in oneembodiment, just prior to use, an iontophoresis solution may be bufferedto a neutral pH with sodium bicarbonate or some other buffer.

In some embodiments, where a buffer is included in an iontophoresissolution, the solution may also include a higher lidocaine concentrationthan in previously used solutions. Since a buffer may slow the rate atwhich the solution is driven across the TM, increasing the lidocaineconcentration may make up for this slowing by increasing the percentageof ionized lidocaine molecules in the buffered iontophoresis solution.For example, an unadjusted iontophoresis solution may comprises asolution of 1:2000 epinephrine and 2% lidocaine HCl, having a pH betweenapproximately 5.2-5.9. When the solution is buffered to a neutral pH ofabout 7, the degree of ionization of lidocaine will decrease. Sinceiontophoresis uses electrical current to push ionized molecules across abiological membrane such as the TM, the buffering will cause a decreasein lidocaine flux due to the increased pH. One way to balance thisdecrease in iontophoresis transport is to increase the amount of ionizedmolecules in the starting solution by increasing the concentration oflidocaine. For example, if the iontophoretic solution started with a3.3% lidocaine HCl concentration instead of 2%, then even a loss of 20%of the ionized molecules by raising the pH to 7, will result in asolution having a 2.6% lidocaine HCl concentration. Accordingly, invarious embodiments, the solution may have up to 4% lidocaine HCl, asthis amount has been determined to be safe for iontophoretic purposes.In some embodiments, the amount of epinephrine in solution may also beadjusted.

In one embodiment, an iontophoresis system may be configured to delivera maximum output per channel of about 30 volts. In one embodiment, aniontophoresis system may be configured to monitor the actual currentoutput and calculate the charge delivered. In one embodiment, outputcurrent may be monitored in a fault-tolerant manner. For this, theoutput current may be compared to the intended current several times asecond. Then when the measured output current is outside of theallowable range, a “strike” is recorded. If a certain number of strikesaccumulates within a block of time, the user may be alerted that thesystem needs to be checked.

In one embodiment of an iontophoresis method, the current beingdelivered to each channel may be ramped up in steps, such that thecurrent set point is raised to a value, maintained for a certain amountof time, and then raised again. This method of ramping the current up ordown may help facilitate current monitoring. In another embodiment,output of the iontophoresis device may be recorded. For example, outputvoltage, output current, and/or setpoint current of each channel may besent to a data acquisition system and recorded over the course of theprocedure, without interfering with the current supplied to the patient.In one embodiment, from this data, changes in body resistance and poweroutput may be calculated.

In one embodiment, an iontophoresis system may further be configured torecord patient discomfort continuously over the course of the procedureusing a sensometer as shown in FIG. 3. As shown in FIG. 3, the patientcan adjust a dial 402 or slider 404, which can correspond to a painlevel. The scale can use a numeric range as in dial 402 or a more userfriendly scale that shows a face pain scale may be used. The dial orslider is attached to a potentiometer such that the output voltage orcurrent is correlated with a pain level. Patient discomfort could becompared second by second with the electrical output to better informsubsequent current delivery settings to reduce patient discomfort. Thesensometer can be operatively connected with the iontophoresisgenerator. The iontophoresis generator could then monitor the patient'slevel of discomfort and adjust the output accordingly, such astemporarily reducing output current until the patient felt better. Thedata may be recorded alongside the output of the iontophoresis machine.

The present invention may be embodied in other specific forms withoutdeparting from the essential characteristics thereof. These otherembodiments are intended to be included within the scope of the presentinvention, which is set forth in the following claims.

1. A method of anesthetizing a tympanic membrane of an ear of a patientusing iontophoresis, the method comprising: delivering an anesthetizingdrug solution to an ear canal of the patient's ear, wherein the drugsolution includes an anesthetic and a buffer, and wherein the drugsolution has a pH in the range of about 6.5 to about 7.5; and applyingan amount of current to the drug solution, wherein the amount of appliedcurrent is increased at a rate of less than about 0.5 milliamps persecond until a maximum current is achieved.
 2. The method of claim 1,wherein the anesthetic comprises lidocaine and the buffer comprisessodium bicarbonate, and wherein the solution further comprisesepinephrine.
 3. The method of claim 2, wherein the drug solutionincludes approximately 2%-4% lidocaine by weight.
 4. The method of claim3, wherein the drug solution includes approximately 0.5%-1.0% sodiumbicarbonate by weight.
 5. The method of claim 1, wherein the drugsolution has a pH range of about 6.8-7.2.
 6. The method of claim 1,wherein applying the current comprises increasing the amount of appliedcurrent at a rate of about 0.2 milliamps per second.
 7. The method ofclaim 1, wherein applying the current comprises applying a maximumcurrent of approximately 1.0 milliamp or less.
 8. The method of claim 7,wherein applying the current comprises applying a maximum current ofapproximately 0.8 milliamps or less.
 9. A method of anesthetizing atympanic membrane of an ear of a patient using iontophoresis, the methodcomprising: adding buffer to an anesthetizing drug solution foriontophoresis, wherein the drug solution with added buffer has a pH inthe range of about 6.5 to about 7.5; delivering the bufferedanesthetizing drug solution to an ear canal of the patient's ear; andapplying an amount of current to the drug solution, wherein the amountof applied current is increased at a rate of less than about 0.5milliamps per second until a maximum current of less than about 0.5milliamps is achieved.
 10. The method of claim 9, wherein the buffereddrug solution has a pH range of about 6.8-7.2.
 11. The method of claim9, wherein applying the current comprises increasing the amount ofapplied current at a rate of about 0.2 milliamps per second.
 12. Themethod of claim 9, wherein applying the current comprises applying amaximum current of approximately 0.8 milliamps or less.
 13. A method oftreating a patient, the patient having a first and a second ear canal,the method comprising: positioning a fluid in the first ear canal, thefluid comprising a therapeutic agent; positioning a fluid in the secondear canal, the fluid comprising a therapeutic agent; inserting a firstelectrode of an iontophoresis device in the first ear canal; inserting asecond electrode of the iontophoresis device in the second ear canal;attaching one ground electrode of the iontophoresis device to thepatient, the first electrode and the one ground electrode forming afirst circuit, the second electrode and the same one ground electrodeforming a second circuit; applying the agent from the fluid to a targettissue in the first ear canal by energizing the first circuit to delivera current to the agent in the first ear canal; and applying the agentfrom the fluid to a target tissue in the second ear canal by energizingthe second circuit to deliver a current to the agent in the second earcanal, independently of said applying in said first circuit.
 14. Themethod of claim 13, wherein the agent comprises an anesthetic.
 15. Themethod of claim 13, wherein the agent comprises at least one oflidocaine, epinephrine, sodium bicarbonate, other anesthetics, otherbuffers, or combinations thereof.
 16. The method of claim 13, whereinthe agent comprises at least one of an antibiotic, an anti-inflammatory,a mucolytic, an anesthetic, a steroid, an anti-viral, a surfactant orcombinations thereof.
 17. The method of claim 13, wherein saidenergizing said first or said second circuit comprises applying acurrent to the agent over a time period, said current having an initialvalue, a final value, a ramp-up rate from said initial value to saidfinal value and a ramp-down rate from said final value to said initialvalue.
 18. The method of claim 17, wherein said ramp-up rate is about0.2 milliamps per second.
 19. The method of claim 18, wherein saidramp-up rate comprises a stepped and positive slope.
 20. The method ofclaim 19, wherein said final value is less than about 1.0 milliamp.21-34. (canceled)